Structural aberrations (dysplasia-carcinoma sequence) during neoplastic transformation typically occur relatively late in the process of carcinogenesis with the earlier stages generally silent from a pathological perspective. From a clinical perspective (e.g., in cytological diagnosis), it is desirable to identify earlier stages of carcinogenesis. At early stages, genetic/epigenetic changes may not yet have translated into microscopic consequences, although the fundamental nanoscale architecture of these cells may be perturbed during early neoplastic transformation.
Physical and technological limitations have stymied understanding of changes in cell organization at a submicron scale (e.g., at the nanoscale). For example, the capability of existing optical imaging techniques may be restricted by diffraction-limited resolution. In addition, available imaging techniques are typically unable to quantitatively characterize nanoscale organization of living cells and tissue in a nondestructive manner.
Colorectal cancer remains one of the leading causes of cancer mortality in the United States. In 2006, there were approximately 55,170 estimated colorectal cancer (CRC) related deaths. Given early detection, early-stage colorectal cancer can be curable. However, given the nature of colonic neoplasia, most patients are diagnosed when the cancer has evolved to a more advanced stage thus underscoring the need for effective screening of the at-risk population (e.g., those over 50 years of age) for early detection. For example, existing colorectal cancer screening methods include fecal blood tests (FOBTs), endoscopy for direct visualization of the colon (e.g., flexible sigmoidoscopy or colonoscopy), and/or air-contrast barium enema. Although, the existing methods have demonstrated some efficacy in reducing colorectal cancer mortality and incidence, a large portion of the population do not undergo any endoscopic screening potentially due to patient and/or physician reluctance.
However, due to resource constraints and potential complications, performing colonoscopy on an entire at-risk population (e.g., those over the age of 50) may be impractical. In addition, for the general population the lifetime risk of developing CRC is approximately 6%. Thus performing colonoscopy on a large population to reach a relatively small subgroup of the at risk population who may develop colonic neoplasia is cost and time inefficient. Numerous techniques have been introduced for colorectal cancer screening but have yet to demonstrate the robustness suitable for population screening. For example, reports of demonstrated performance of fecal DNA analysis were not statistically significant in multicenter trials. Further, the marked cost of fecal DNA analysis may be a barrier to wide spread usage. From a radiological perspective, in single center studies, computed tomography colography (virtual colonoscopy) showed promise; unfortunately, the sensitivity demonstrated in multicenter trials have been unreliable.
Thus, there is a need to identify patients with a higher likelihood of harboring colonic neoplasia to provide colonoscopy to a better defined set of patients more likely to be harboring neoplasia thereby sparing those patients who are unlikely to benefit from the cost, inconvenience, and potential complication of colonoscopy.
In addition, pancreatic cancer is another leading cause of cancer death in the United States with most cancers diagnosed at a late, incurable stage. Existing approaches, including high-resolution imaging (MRI, CT, etc.), molecular diagnostics, and/or endoscopic cholangiopancreatography (ERCP), have not demonstrated the robustness for detecting early pancreatic neoplasm for allowing effective treatment.
Current imaging modalities as well as ERCP utilize detection of the presence of a mass lesion, and, therefore the detected tumors are typically biologically too advanced for cure. Despite years of research no clinically adequate molecular markers have been developed. The only route that currently has the potential for diagnosing pre-invasive cancer is through the pancreatic duct, where 90% of adenoma or carcinomas of the pancreas originate. Due to the potential for complications including pancreatitis (3-5% cases), as currently performed, ERCP may not be suitable for routine screening over successive points in time.